Permanent interstitial brachytherapy (PIB) for early stage organ-confined prostate cancer involves permanent surgical implantation of about 100 radioactive sources into the prostate so that a therapeutic radiation dose can be delivered to the cancer cells while minimizing the doses to the surrounding normal tissues. Potential advantages of this approach include continuous irradiation of cancer cells which reduces the impact of cell- cycle dependent variations in cellular radiosensitivity; reduced dose to normal tissues, which allows escalation of tumor dose for increased tumor control; use of a one-time implant procedure, which is more convenient for patients than the fractionated daily treatments of external beam radiotherapy (EBRT) that often last more than six weeks; and the avoidance of potentially detrimental geometric misses caused by the uncertainties in daily patient setup and by inter- and intra-fractional organ motions in EBRT. To fully achieve the potential of PIB, one must be able to accurately place these sources in a pre-designed spatial pattern for producing adequate tumor coverage and must maintain the initial source positions during the protracted PIB dose delivery, in addition to having an accurate characterization of the dosimetric properties of each source. In prostate PIB, however, variation in post-implant source position is inevitable because edema induced by the surgical procedure causes the prostate gland to swell rapidly (to as large as twice of its pre-surgery volume) followed by a gradual resolution that can require more than a month. A number of recent studies have shown that edema-induced variations in prostate volume and source positions can lead to large variations in the dose delivered to the tumor, which, if ignored, can have detrimental consequences for patients developing moderate or severe edema. This has become an especially urgent issue with the recent introduction and clinical application of a new 131Cs source, which has a shorter radioactivity decay half-life (9.7 day) than radionuclides used previously and therefore is more sensitive to the edema-induced source position variations. The specific aims of this project are: 1) to develop a new and integrated approach for accurate determination of the dosimetric effects of edema so that effective therapeutic intervention strategies can be designed and integrated into the planning and treatment of PIB with or without radiobiology guidance; 2) to conduct a systematic validation of the proposed approach and the existing edema models using the histories of edema evolution measured for 15 PIB patients; and 3) to perform a comprehensive evaluation of the clinical significance of edema-induced dosimetric variations and the effectiveness of therapeutic intervention strategies so that the efficacy of PIB can be optimized for each individual patient. We hypothesize that the successful completion of this project will enable effective clinical management of the effects of prostate edema for each patient and thereby help to achieve the full potential of PIB in the treatment of early-stage prostate cancer. Public Health Relevance: Permanent implantation of radioactive seeds containing iodine-125, palladium-103, or cesium-131 in the prostate, also called brachytherapy, has become a popular form of radiation therapy for carefully selected prostate cancer patients. The clinical success of brachytherapy is highly dependent on the ability to properly plan the procedure, implant the radioactive source, and perform dosimetry in a way that ensures that the radiation dose distributions are well defined and appropriate for optimal treatment of the tumor. This ability, however, has been hampered by the inevitable development and resolution of surgery-induced prostate edema, which can last over a month. The primary objective of this project is to develop a new method to consider the effects of edema in radiation dosimetry and treatment planning so that the efficacy of this therapy can be optimized for each patient. [unreadable] [unreadable] [unreadable]